Heart Failure
Conditions
Interventions
Product Name: TRV027
Product Code: TRV027
Pharmaceutical Form: Injection
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use
Sponsors
Trevena Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients may be included in the study if all of the following criteria are met: 1. Men or women aged =21 years and = 85 years a. Women of non-child-bearing potential must have: i. Documentation of surgical sterilization (hysterectomy and/or bilateral oophorectomy) OR ii. Experienced menopause: no menses for >12 months b. Women of child bearing potential must have a: i. A negative pregnancy test, AND ii. Have had their most recent menstrual period = 2 weeks prior to presentation 2. Able to provide written informed consent 3. Reported pre-existing diagnosis of heart failure with no hospitalization for heart failure within 30 days prior to screening. Heart failure must be treated for at least 30 days prior to screening with daily oral loop diuretics plus ACE inhibitors and/or beta-adrenergic blockers for patients for whom ACE inhibitors and betaadrenergic blockers are not documented as contraindicated. 4. Systolic blood pressure =105 mmHg and =160 mmHg within 30 minutes of randomization 5. Ventricular rate =125 bpm. Patients with rate-controlled persistent or permanent atrial fibrillation (aFib) at screening are permitted. 6. Presence of ADHF defined by: o BNP > 400 pg/mL or NT-proBNP > 1600 pg/mL ? For patients with BMI >30 kg/m2: BNP > 200 pg/mL or NT-proBNP > 800 pg/mL ? For patients with rate-controlled persistent or permanent aFib: BNP > 600 pg/mL or NTproBNP > 2400 pg/mL o AND congestion on chest radiograph (CXR) o AND at least two (2) of the following: ? Rales by chest auscultation ? Edema = +1 on a 0-3+ scale, indicating indentation of skin with mild digital pressure that requires 10 or more seconds to resolve in any dependent area including extremities or sacral region. ? Elevated jugular venous pressure (=8 cm H2O) 7. Receipt of a IV loop diuretic at a minimum dose 40 mg furosemide (or equivalent loop diuretic) for the treatment of dyspnea due to ADHF at least 1 hour prior to anticipated randomization and the initiation of study medication 8. Patient report of dyspnea at rest or upon minimal exertion during screening at least one hour after administration of IV loop diuretic. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 155 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 465
Exclusion criteria
Exclusion criteria: Patients will be excluded if any of the following apply: 1. Women who are pregnant or breast-feeding 2. Clinical presentation: a. Suspected acute coronary syndrome (ACS) based on clinical judgment. NOTE: the presence of elevated troponin concentrations in the absence of other clinical findings, is not sufficient for a diagnosis of ACS b. Coronary revascularization in the 3 months prior to screening or planned during current admission c. Temperature >38.5oC (oral or equivalent) or suspected sepsis or active infection requiring IV antimicrobial treatment d. Clinically significant anemia (hematocrit 145 mEq/L (145 mmol/L) f. Current or planned ultrafiltration, paracentesis, thoracentesis, hemofiltration or dialysis at time of screening g. Any mechanical ventilation requiring tracheal intubation and sedation at the time of screening or during the current hospitalization h. CPAP/BiPAP discontinued less than 1 hour prior to randomization, unless prescribed for treatment of sleep apnea and used for >3 months i. History or current use of left ventricular assist devices (LVADs) or history of use of an intra-aortic balloon pump (IABP) within the last year j. Administration of intravenous radiographic contrast agent within 72 hours prior to screening or presence of acute contrast induced nephropathy at the time of screening k. Presence of clinically significant arrhythmia that, in the Investigator’s opinion, is the primary cause of worsening heart failure symptoms, including ventricular tachycardia or bradyarrhythmia with ventricular rate 0.1 mg/kg/hr or equivalent) or any IV nitrates if the patient’s screening systolic blood pressure is 2.5 mcg/kg/min dopamine), within 48 hours prior to randomization or any use of IV inotropes or vasopressors within 2 hours prior to randomization d. Use of angiotensin receptor blocking drugs (ARBs) within 7 days of prior to randomization. Angiotensin converting enzyme (ACE) inhibitors are permitted. e. Use of any investigational medication within 30 days or 5 terminal elimination half-lives (whichever is longer) prior to randomization f. As determined by the Investigator, clinically significant hypersensitivity or allergy to, or intolerance of, angiotensin receptor blockers 4. Medical history: a. Any significant pulmonary disease that requires steroids IV or inhalation therapy, that is known to significantly affect pulmonary function tests or led in the past to respiratory failure b. Major surgery within 8 weeks prior to screening c. Stroke within 3 months prior to screening d. eGFR (sMDRD) 75 mL/min/1.73m2 between presentation and randomization e. Post cardiac or renal transplant f. Listed for renal transplant or cardiac transplant with anticipated transplant time to transplant < 6 months g. History of severe left ventricular outlet obstruction (either valvular or sub-valvular), severe mitral valve stenosis or any other surgically correctable valvular disease as the primary cause of AHF, with the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the overall safety and efficacy of TRV027 when administered in addition to standard of care (SOC) on mortality, morbidity, dyspnea, and length of stay in patients hospitalized with Acute Decompensated Heart Failure (ADHF). ;Secondary Objective: To evaluate the efficacy of TRV027when administered in addition to SOC in relieving dyspnea and congestion in patients with ADHF. ;Primary end point(s): The primary clinical endpoint is a composite of the following outcomes: (1) time from randomization to death through day 30, (2) time from randomization to heart failure re-hospitalization through day 30, (3) time from randomization to worsening heart failure (WHF, see Section 6.4) through day 5, (4) change in dyspnea VAS score (calculated area under the curve) from baseline through day 5, and (5) length of initial hospital stay (in days) from randomization. The component outcomes will be combined by deriving an average Z for each patient. ;Timepoint(s) of evaluation of this end point: 30 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints are (1) The change in dyspnea VAS scores (calculated area under the curve representing the change from baseline over time) from baseline through day 5, (2) the change in centrally-measured NT-proBNP from baseline to 48 hours, and (3) average Z comprising the components of the primary endpoint and incorporating changes in troponin-T and cystatin-C from baseline to 48 hours. ;Timepoint(s) of evaluation of this end point: Day 5 | — |
Countries
Argentina, Bulgaria, Canada, Czech Republic, Germany, Hungary, Israel, Poland, Romania, Russian Federation, Slovakia, United States
Contacts
Public ContactPamela Swiggard
Trevena Inc.
Outcome results
None listed